1IJY: Crystal Structure of the Cysteine-rich Domain of Mouse Frizzled 8 (Mfz8)

Citation:
Abstract
Members of the Frizzled family of seven-pass transmembrane proteins serve as receptors for Wnt signalling proteins. Wnt proteins have important roles in the differentiation and patterning of diverse tissues during animal development, and inappropriate activation of Wnt signalling pathways is a key feature of many cancers. An extracellular cysteine-rich domain (CRD) at the amino terminus of Frizzled proteins binds Wnt proteins, as do homologous domains in soluble proteins-termed secreted Frizzled-related proteins-that function as antagonists of Wnt signalling. Recently, an LDL-receptor-related protein has been shown to function as a co-receptor for Wnt proteins and to bind to a Frizzled CRD in a Wnt-dependent manner. To investigate the molecular nature of the Wnt signalling complex, we determined the crystal structures of the CRDs from mouse Frizzled 8 and secreted Frizzled-related protein 3. Here we show a previously unknown protein fold, and the design and interpretation of CRD mutations that identify a Wnt-binding site. CRDs exhibit a conserved dimer interface that may be a feature of Wnt signalling. This work provides a framework for studies of homologous CRDs in proteins including muscle-specific kinase and Smoothened, a component of the Hedgehog signalling pathway.
PDB ID: 1IJYDownload
MMDB ID: 17009
PDB Deposition Date: 2001/5/1
Updated in MMDB: 2007/10
Experimental Method:
x-ray diffraction
Resolution: 1.35  Å
Source Organism:
Similar Structures:
Biological Unit for 1IJY: dimeric; determined by author
Molecular Components in 1IJY
Label Count Molecule
Proteins (2 molecules)
2
Frizzled Homolog 8(Gene symbol: Fzd8)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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